title: T cell-independent modulation of experimental autoimmune encephalomyelitis in ADAP-deficient mice.
abstract: The adhesion- and degranulation-promoting adaptor protein (ADAP), expressed in T cells, myeloid cells, and platelets, is known to regulate receptor-mediated inside-out signaling leading to integrin activation and adhesion. In this study, we demonstrate that, upon induction of active experimental autoimmune encephalomyelitis (EAE) by immunization with the myelin oligodendrocyte glycoprotein35-55 peptide, ADAP-deficient mice developed a significantly milder clinical course of EAE and showed markedly less inflammatory infiltrates in the CNS than wild-type mice. Moreover, ADAP-deficient recipients failed to induce EAE after adoptive transfer of myelin oligodendrocyte glycoprotein-specific TCR-transgenic T cells (2D2 T cells). In addition, ex vivo fully activated 2D2 T cells induced significantly less severe EAE in ADAP-deficient recipients. The ameliorated disease in the absence of ADAP was not due to expansion or deletion of a particular T cell subset but rather because of a strong reduction of all inflammatory leukocyte populations invading the CNS. Monitoring the adoptively transferred 2D2 T cells over time demonstrated that they accumulated within the lymph nodes of ADAP-deficient hosts. Importantly, transfer of complete wild-type bone marrow or even bone marrow of 2D2 TCR-transgenic mice was unable to reconstitute EAE in the ADAP-deficient animals, indicating that the milder EAE was dependent on (a) radio-resistant nonhematopoietic cell population(s). Two-photon microscopy of lymph node explants revealed that adoptively transferred lymphocytes accumulated at lymphatic vessels in the lymph nodes of ADAP-deficient mice. Thus, our data identify a T cell-independent mechanism of EAE modulation in ADAP-deficient mice.
authors.affiliation: Institute of Molecular and Clinical Immunology, Otto von Guericke University, 39120 Magdeburg, Germany;
authors.forename: Swen
authors.initials: S
authors.lastname: Engelmann
authors.forename: Mauro
authors.initials: M
authors.lastname: Togni
authors.forename: Anja
authors.initials: A
authors.lastname: Thielitz
authors.forename: Peter
authors.initials: P
authors.lastname: Reichardt
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kliche
authors.forename: Dirk
authors.initials: D
authors.lastname: Reinhold
authors.forename: Burkhart
authors.initials: B
authors.lastname: Schraven
authors.forename: Annegret
authors.initials: A
authors.lastname: Reinhold
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency*; D019264:Adoptive Transfer; D000818:Animals; D016026:Bone Marrow Transplantation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C491468:Fyb protein, mouse; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55)